Sleep disorders are commonly underdiagnosed and are a significant source of concern in the geriatric population.[1] Several diverse factors may contribute to sleep disturbances in a large percentage of the elderly population. These include retirement, health problems, death of spouse/family members, and changes in circadian rhythm.[2, 3] Changes in sleep patterns may be part of the normal aging process; however, many of these disturbances may be related to pathological processes that are not considered a normal part of aging.[1, 2]
In addition to affecting quality of life—because of excessive daytime sleepiness, as well as physical, psychological, and cognitive problems—sleep disorders have been implicated with increased mortality.[4, 5] In addition, the number of medications used tends to increase with age, which in itself can lead to increased morbidity, mortality, and side effects such as falls,[6] cognitive impairment, and even sleep disturbances.[7]
When a person experiences significant and prolonged sleep disturbance, they will generally contact their primary care provider for an evaluation. This evaluation may consist of a medical history review, concomitant medications, physical examination, lab work, and a Mental Status Examination. If the provider is unable to determine the underlying causality of the sleep disturbance, referral to a psychiatrist or sleep specialist may be necessary. At this point, a more in-depth examination is performed to rule out other potential contributing factors and to reach a diagnosis. Determining the causality of the sleep disturbance is imperative to be able to educate patients and caregivers about treatment alternatives.
Treating insomnia in the elderly can improve overall health, but care must be taken when medications are used in this particular population.[1] Treatments for insomnia include over-the-counter and prescription medications. However, non-medication treatment options are preferred and may lead to more durable benefits. Non-medication treatments include behavioral modification, relaxation techniques, sleep hygiene improvement, sleep restriction, light therapy,[8] cognitive-behavioral therapies,[1, 9] mindfulness,[9] smartphone applications,[9] tai chi, yoga, meditation, acupuncture, and acupressure.[10] There is even an FDA-approved bedside device for insomnia that cools and pumps fluid to a forehead pad that is worn throughout the night. The device helps reduce latency to stage 1 and stage 2 sleep.[11]
Normal sleep is organized into different stages that cycle throughout the night. Polysomnographic studies have classified the sleep stages into rapid-eye-movement (REM) sleep and non-REM sleep.
REM sleep (ie, paradoxical desynchronized sleep) is the stage of sleep during which muscle tone decreases markedly; this stage is associated with bursts of conjugate gaze and dreaming. Relative amounts of REM sleep are maintained until extreme old age, when they show some decline.
Non-REM sleep is subdivided into 4 stages. Stages 1 and 2 constitute light sleep, and stages 3 and 4 are called deep sleep or slow-wave sleep (SWS). With aging, an increase in the duration of stage 1 sleep and an increase in the number of shifts into stage 1 sleep occur. Stages 3 and 4 decrease markedly with age; in extreme old age (> 90 years), stages 3 and 4 may disappear completely. Some studies, however, have found that elderly women tend to have normal or even increased stage 3 sleep, whereas men have normal or reduced stage 3 sleep.
Time in bed
Older individuals spend more time lying in bed at night without attempting to sleep or unsuccessfully trying to sleep. They also use the bed for resting and napping during the day.
Total sleep period
Total sleep period refers to the time from sleep onset to the final awakening from the main sleep period of the day. Total sleep period increases with age because of the increase in the number of awakenings.
Total sleep time
Total sleep time refers to the total sleep period minus the time spent awake during the sleep period. Studies have found the total sleep time to be either reduced or unchanged in the older population.
Sleep latency
Sleep latency is the time from the decision to sleep to the onset of sleep. Studies have found considerable variability in individuals. In females, sleep latency has been related to increases in age and hypnotic drug use, which would decrease sleep latency.
Wake after sleep onset
Wake after sleep onset is the time spent awake from sleep onset to final awakening. An increase occurs in the time spent awake after sleep onset in the older population. Webb was able to attribute 38% of nocturnal arousals in a study to physical discomfort (eg, bladder distention, urinary urgency).[12] Pain, restless legs, and dyspnea have also been identified as factors in arousal during sleep.
Sleep efficiency
Sleep efficiency is the ratio of total sleep time to nocturnal time in bed. Most studies have found sleep efficiency to be decreased in the older population.
Nocturnal penile tumescence
Studies have shown that a gradual decline in nocturnal penile tumescence (NPT) during REM sleep occurs with age, even though the duration of REM sleep remains fairly constant until extreme old age.
Few data describe cardiovascular changes during sleep in the older population. One study found that auditory awakening thresholds from stage 4 sleep were significantly lower during the first night's sleep in a sleep laboratory in older men than in younger men.[13]
Older people spend more time in bed to get the same amount of sleep they obtained when they were younger; however, the total sleep time, at most, is only slightly decreased, with an increase in nocturnal awakenings and daytime napping. They often report having earlier bedtimes and an increased sleep latency (time to fall asleep), but excessive daytime somnolence is not part of normal aging. Older persons have been observed to be more easily aroused from sleep by auditory stimuli, suggesting increased sensitivity to environmental stimuli. Increasing age is associated with a weakening and decrease in responsiveness to circadian rhythms.[14]
Two primary sleep disorders that increase with age are obstructive sleep apnea (OSA) and periodic limb movements in sleep (PLMS).
OSA is the lack of breathing during sleep, and it can be obstructive (upper airway occlusion), central (primary neurologic disease), or mixed. People with OSA may experience waking with gasping, confused wandering in the night, and thrashing during sleep.
Because waking resolves OSA, avoid sedatives and hypnotics in these patients because such agents can further relax the pharynx dilators, thereby worsening the apnea. Martin et al found that among healthy older adults living in community settings, the prevalence of OSA (defined by more than 5 apneas per hour) was 28% in men and 20% in women.[15] They also found that among a random sample of patients in a medical ward, the prevalence of OSA was higher (33%).[15] This may be because of the high incidence of congestive heart failure (CHF) in this group. Significantly, many elderly inpatients are prescribed hypnotics, which can exacerbate OSA. OSA occurs in 42% of people with dementia who live in nursing homes and correlates with cognitive function. In the general population, prevalence of OSA may be as high as 49% in advanced ages.[16]
An interaction between OSA and the cognitive deterioration of dementia is likely.[17, 18, 19, 20] Sedative-hypnotic medications will likely exacerbate sleep apnea and are not recommended in patients with OSA. OSA can result in daytime hypersomnolence, systemic hypertension, cardiac arrhythmias, cor pulmonale, and sudden death. Risk of coronary artery disease is also increased.[21] OSA has also been associated with increased cancer prevalence due to nocturnal hypoxia.[22]
PLMS, or nocturnal myoclonus, is repetitive, unilateral, or bilateral stereotyped leg jerks that arouse the patient from sleep. In a random sample of 427 older volunteers, 45% had PLMS; this statistic correlated with dissatisfaction with sleep, sleeping alone, and kicking at night. Other studies have assessed prevalence of PLMS as 28.6% in a sample of 2162 subjects and 29.3% in a random sample of 696 individuals.[23, 24] The incidence of nocturnal myoclonus increases with age, and the likelihood of an associated sleep-wake The incidence of nocturnal myoclonus increases with age, and the likelihood of an associated sleep-wake complaint is related to the absolute number and intensity of the leg movements.
Sundown syndrome is a behavioral phenomenon closely related to disturbed circadian rhythms[25] with incident rates of up to 66% in patients with dementia and those in nursing homes.[26, 27, 28, 29] Disrupted circadian rhythms causing sundown syndrome may be associated with a seasonal pattern (ie, winter weather or geographic locations receiving less sun).[30] Behaviorally, it is characterized by agitation, aggression, confusion, disorientation, and mood disturbances.[28, 31] Its name, “sundowning,” reflects that it is typically observed in the late afternoon or evenings. Sundowning behaviors have been associated with functional impairment, rapid decline of cognition, financial toll, caregiver burden, and an increased risk of institutionalization.[29, 32, 33]
Psychiatric illnesses such as dementia. anxiety, and depression are often associated with insomnia.[34, 35, 36, 37] Of elderly patients with major depressive disorders, 50% report substantial sleep impairment. Clinical tools such as the Mini–Mental State Examination (MMSE) and/or Geriatric Depression Scale (GDS) should be used to evaluate for these disorders. An attempt should be made to manage the underlying condition before initiating treatment for sleep.
A patient who is depressed may experience an increase in sleep latency, a decrease in REM latency, prolonged initial rapid-eye-movement (REM) sleep, an increase in nighttime wakefulness, a decrease in slow-wave sleep (SWS), and early-morning awakening.
Patients with dementia, especially those with Alzheimer disease, have lower sleep efficiency; an increase in the length of stage 1 sleep; a decrease in stage 3, stage 4, and REM sleep; more sleep disruptions and awakenings; episodes of nocturnal wandering; and an increase in daytime napping.[38]
Personality and affective disorders can lead to poor sleep or subjective complaints of poor sleep. This can further manifest as early-morning wakefulness, a reduction of stage 4 sleep, and short REM latency, which is more pronounced in the older population. Bipolar disorders, schizophrenia, posttraumatic stress disorder (PTSD), and anxiety disorders can result in difficulty initiating and/or maintaining sleep.
Older patients take an average of 5–9 daily medications, some of which can interfere with sleep and wakefulness. Sedative antidepressants (eg, amitriptyline) and sedative neuroleptics (eg, chlorpromazine, clozapine) can cause impaired performance and daytime drowsiness. Avoid amitriptyline in older patients because of the anticholinergic effects and possible confusion. Beta-blockers, especially lipophilic compounds (eg, metoprolol, propranolol), can cause difficulty falling asleep, an increased number of awakenings, and vivid dreams; choosing beta blockers with lower lipophilicity (eg, bisoprolol, atenolol) is crucial to minimizing sleep disturbances.[39]
The chronic use of sedative-hypnotics often confounds normal sleep-wake functioning because of drug-withdrawal effects or daytime drowsiness. Significant numbers of hospitalized older patients receive inappropriate sedative-hypnotic prescriptions.[40] Additionally, the xanthines theophylline and caffeine are stimulants that increase wakefulness while decreasing SWS and total sleep time. The effect of caffeine can last as long as 8–14 hours and may be more pronounced in older patients because of decreased caffeine clearance with decreased liver function. Furthermore, caffeine is present in many over-the-counter medications, including analgesics, cold or allergy remedies, and appetite suppressants.
Nicotine is also a stimulant and affects sleep in a manner similar to that of caffeine. Several studies have shown that people of all ages who smoke have more sleep disturbances than people who do not smoke, primarily difficulty falling asleep and decreased sleep duration. Excessive daytime sleepiness may also be seen in those who smoke.[41]
Other causes of sleep disorders in geriatric patients include the following:
As many as 50% of elderly people have insomnia-like symptoms.[43, 44] Sleep disturbance or insomnia is the third most common patient complaint, ranking behind headaches and the common cold. Approximately 15% of the adult population in the United States has insomnia of significant enough severity to seek medical attention. Of the US population, 1.7% receive a hypnotic prescription annually, and another 0.8% purchase nonprescription sleep aids. Fifty million Americans occasionally take some form of sleep medication. In one study of 649 adults, use of prescription sleep aids was found to be as high as 19%.[45]
Older women are more likely to experience insomnia than older men. In a large epidemiologic study of people older than 70 years, 35% of women reported moderate to severe insomnia, compared to only 13% of men.[46] More than one half of people older than 64 years who live at home and two thirds of people older than 64 years who reside in a long-term care facility are estimated to have some form of sleep disturbance. Additionally, poor sleep is regarded as a risk factor for long-term care facility placement.[47]
In addition to affecting quality of life, sleep disorders have been associated with increased mortality. Two primary sleep disorders that increase with age are obstructive sleep apnea (OSA) and periodic limb movements in sleep (PLMS). OSA can result in daytime hypersomnolence, systemic hypertension, cardiac arrhythmias, cor pulmonale, and sudden death. In a random sample of 427 older volunteers, 45% had PLMS, and they reported dissatisfaction with sleep, sleeping alone, and kicking at night. Furthermore, PLMS is associated with greater risk of depression, anxiety, and dementia.[48] Yaffe et al suggested that older women with sleep-disordered breathing (SDB), characterized by recurrent arousals from sleep and intermittent hypoxemia, have an increased risk of developing cognitive impairment.[49]
In a study of SDB and nocturnal cardiac arrhythmias in older men, Mehra et al found that the likelihood of atrial fibrillation or complex ventricular ectopy (CVE) increased along with the severity of SDB. In addition, different forms of SDB were associated with the different types of arrhythmias.[50] In a study of 697 veterans, patients with moderate-severe SDB had twice the odds of having nocturnal cardiac arrythmias.[51]
Polysomnography in 2911 participants showed that the odds of atrial fibrillation and of complex ventricular ectopy increased with increasing quartiles of the respiratory disturbance index (a major index including all apneas and hypopneas). Central sleep apnea was more strongly associated with atrial fibrillation than with complex ventricular ectopy. In contrast, obstructive sleep apnea and hypoxia were associated with complex ventricular ectopy; participants in the highest hypoxia category had an increased odds of CVE compared with those in the lowest quartile. The results suggest that different sleep-related stresses may contribute to atrial and ventricular arrhythmogenesis in older men.[50] In a study of 2350 older men, a relationship between sleep-related reduced sympathovagal balance and increased atrial ectopy was also observed, with both independently associated with a future atrial fibrillation; the relationship was significantly modified by obstructive apnea.[52]
Individuals should be made aware that obtaining 8 hours of sleep per night is not crucial. Rather, sleep needs are individualized. Although one person may need 9 hours of sleep, another person may need only 5 hours. The amount of sleep required may also change with age. If a significant change in amount of sleep occurs but there are no disturbances in daily functioning, there should not be a cause for concern. When significant disturbances in daily functioning have occurred, it is important to identify the cause of the sleep disturbance and discuss available treatment options.
A variety of treatment options are available for insomnia and do not necessarily include the use of prescription medications. For example, muscle relaxation therapy may be indicated.[53] However, if prescription medications are warranted, there are many to choose from. Certain medications should be avoided in the elderly population (see Medication).
Experts suggest stimulus control,[54] which means using the bed for only sleep and sex. If people are used to reading or watching television in bed, they are encouraged to leave the bedroom and engage in a relaxing activity elsewhere until they are sleepy and ready to return to bed.
Teaching patients muscle-relaxation techniques to reduce tension and promote sleep is also useful. Regardless of the underlying causes of insomnia, general habits should be practiced for good sleep.
Patients should be instructed to go to bed at the same time, wake up at the same time, and avoid daytime napping, caffeine, heavy meals, nicotine, alcohol, and exercise at bedtime. Sedentary elderly persons should be encouraged to start a daily exercise program in the morning, as moderate training (60 min/d) has been shown to improve sleep quality.[55] Another useful tool is to turn the bedroom into an environment that is quiet, dark, and cool and ultimately promotes sleep.
The websites below provide further education on insomnia. These sites have information on signs and symptoms, causality, preventive measures, complications, treatments, and even current enrollment in clinical trials for insomnia.
Evaluation of sleep disorder in elderly patients begins with a complete sleep history. The assessment of includes a detailed multidisciplinary approach. Sleep-related problems in the elderly include hypersomnia, disorientation, delirium, impaired intellect, decreased cognition, psychomotor complaints, increased accidents, and falls.[56] In the geriatric population, the most frequent complaints are problems initiating or maintaining sleep.[57]
Whenever possible, interview the bed partner, because he or she often notices problems with the patient's sleep of which the patient is unaware.
A good sleep history includes questions relating to typical sleep at night; daytime functioning; presence of medical conditions; intake of caffeine, alcohol, drugs, or food before bedtime; and any history of psychiatric and mood disorders.
The following questions may also be considered:
These data help determine the sleep pattern of the patient, the severity of the disorder, and the possible causes leading to sleep disturbances. They also help differentiate between sleep apnea (SA) and PLMS.
Having the patient maintain a sleep diary for several weeks before arriving for assessment is advisable. This provides a reliable perspective about the patient's condition for the clinician, and the patient can learn more about their sleeping patterns.
Remember that individuals with this disorder have an increased lifetime risk for suicide, which is significant.[58] Inquiring about suicidal ideation at each visit is always important. In addition, the interviewer should inquire about past acts of self-harm or violence.
Ask the following types of questions when determining suicidal ideation or intent:
If the reply is positive for these thoughts, inquire about specific plans, suicide notes, family history (anniversary reaction), impulse control and access to firearms. If the patients has suicidal thoughts, the chart should document that the patient does not have an immediate plan or that he/she was referred for psychiatric hospitalization.[59]
Inquiring about homicidal ideation or intent during each patient interview is also important.[60] Ask the following types of questions to help determine homicidal ideation or intent:
If the reply to one of these questions is positive, ask the patient if he or she has any specific plans to injure someone and how he or she plans to control these feelings if they occur again.
If the patient has homicidal ideation, refer the patient immediately for psychiatric hospitalization.
Physical examination and the Mental Status Examination may give clues to the causes of sleep disturbance (eg, obesity with resulting obstructive sleep apnea [SA], depression). In addition, potential complications of sleep disorders, such as hypertension from obstructive SA, may also be discovered.
Obtain a complete medical history, and perform a complete Mental Status Examination, physical examination, and neurologic examination to assist with the evaluation and rule out other disease processes.
Because of the variability of the presentation of the disorder, any or all symptoms of insomnia or other sleep disorders may manifest, depending on the presenting subtype. Examples of items to assess in the Mental Status Examination are listed below.
After a detailed history, a clinician may find it necessary to refer the patient to a sleep disorders center for evaluation of sleep apnea. A full-night polysomnogram records brain waves by electroencephalography (EEG); eye movement by electro-oculography (EOG); chin muscle tension and leg movements by electromyography (EMG); heart rate by electrocardiography (ECG); and blood oxygen saturation levels by pulse oximetry. Polysomnography is not recommended as a routine test; however, it can be used for abnormal behaviors during sleep or if treatment fails.[3]
Portable recorders are also used as screening tools. These devices are placed on patients in the afternoon, and patients are then sent home to sleep on their beds at night. These systems are more convenient and less expensive than a laboratory polysomnogram.
Modern consumer devices such as smartwatches or sleep trackers seem to be promising for screening and monitoring sleep-related breathing disturbances.[61, 62, 63] In a 2024 study of 35 community-dwelling older adults (of which 17 had moderate-to-severe obstructive sleep apnea and 10 had periodic leg movement disorder), accurate measurements of heart rate, breathing rate, and breathing disturbance indices could be made using under-mattress trackers.[64] A 2022 study demonstrated effective sleep quantification analysis, including statistically significant abnormal REM, in 20 Parkinson’s disease patients as compared to 18 control patients, when using a smartwatch-based sensor.[65] Of note, in 2024, the Apple Watch received “clearance” by the FDA for marketing of Apple’s Sleep Apnea Notification Features by using sensor data to identify patterns of breathing disturbances that may be suggestive of moderate-to-severe sleep apnea. Nevertheless, large-scale clinical studies are needed to understand clinical adoption and application of wearable devices.
Ferritin levels of less than 50 ng/mL have been found to be present in elderly patients with restless legs syndrome.
The geriatric population is the largest group of people who use hypnotic drugs. People older than 60 years receive 33% of all hypnotic prescriptions, although they constitute only 14% of the population. The use of sedative-hypnotics by the elderly population has been associated with falls, hip fractures, and daytime carryover symptoms. When evaluating a patient, exclude primary sleep disorders and review medications and other contributory medical conditions.
Patient education on age-related changes in sleep and good sleep hygiene may be adequate treatment for many older adults. If the initial history and physical examination findings do not reveal a serious underlying cause, a trial of improved sleep hygiene is the best initial approach.
The common recommended measures include the following:
People who are overweight or obese and habitually snore loudly may be helped by weight loss. All people who snore loudly should abstain from alcohol or other sedatives before going to bed. They should also take measures to avoid supine sleeping (eg, by taping a tennis ball to the back of their bedclothes).
In the absence of obstructive sleep apnea (OSA), contributing conditions, such as allergies, nasal pathology, or nasopharyngeal enlargement, should be sought and adequately managed by intranasal corticoid sprays or evaluated by an ear, nose, and throat specialist. If the sleep problem is secondary to a medical problem, treat the primary problem rather than the sleep problem. Polysomnography is indicated when primary sleep disorders such as SA or periodic limb movements in sleep (PLMS) are suspected.
Consultation with appropriate specialists may be indicated, depending on the underlying causes of the sleep disorder, such as psychiatric consultation for severe depression and pulmonary or surgical consultation for OSA.
Psychologists may provide cognitive-behavioral therapy for insomnia (CBT-I).[66] In a 2014 study of 118 older adults, CBT-I resulted in significant improvements in sleep quality, daytime functioning, and sleep timing (particularly for wake after sleep onset and sleep efficiency) both immediately following treatment and at 3 month follow-up.[67] A 2018 randomized controlled clinical trial of 72 older adults found significantly greater reductions in insomnia (and depression severity) following intervention with CBT-I and CBT-I plus positive mood strategies (ie CBT-I+).[68]
For older patients who are computer savvy, computerized cognitive-behavioral therapy for insomnia (CCBT-I) may be a more attractive approach than the traditional face-to-face therapy sessions. In a meta-analysis, CCBT-I using Internet programs improved several sleep parameters and showed a high treatment adherence rate.[69]
Before any medications are prescribed, the first priority should be to determine the underlying cause of the sleep disorder, rather than just treating insomnia symptomatically. Usually, treatment on a short-term basis together with sleep hygiene is appropriate for transient insomnia, such as insomnia secondary to bereavement or acute hospitalization. Medications used for insomnia in this population include antidepressants, nonbenzodiazepines, a melatonin agonist, and herbals. Medications, if used, should be started with a low dose and monitored for side effects.[70]
According to the American Geriatrics Society (AGS) 2023 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults, barbiturates should be avoided because of the high risk of overdose, even at low dosages, and of physical dependence.[71] Chloral hydrate should also be avoided in older adults because of tolerance within just 10 days of treatment and risk of overdose with doses just 3 times the therapeutic dose.
Benzodiazepines remain the most commonly prescribed agents for sleep, although users of benzodiazepines tend to report poorer quality of sleep than nonusers.[72, 73] According to the 2023 AGS Beers criteria,[71] all benzodiazepines (short-, intermediate-, and long-acting) should not be used for insomnia in older adults. They can increase the risk of cognitive and psychomotor impairments, falls, fractures, and motor vehicle accidents. Use of benzodiazepines in older adults should be limited to other specific indications such as seizure disorders, REM sleep disorders, benzodiazepine or alcohol withdrawal, severe generalized anxiety disorder, periprocedural anesthesia, and end-of-life care. In 2006 Medicare part D excluded benzodiazepines from drug coverage.
The newer nonbenzodiazepine hypnotics zolpidem, zaleplon, and eszopiclone do not cause rebound insomnia or withdrawal symptoms at discontinuation but can have adverse effects similar to benzodiazepines (delirium, falls, and fractures). In a case-crossover study of nursing home residents the nonbenozdiazepine hypnotics were associated with increased risk of hip fracture (OR 1.66) and the risk was even higher for new user (OR 2.20) and residents with cognitive impairment (OR 1.86).[74] These hypnotics should we used with caution in older adults and for no longer than 90 days,[71] even if eszopiclone is approved for prolonged use.
According to the 2023 AGS Beers Criteria, zolpidem should be avoided in patients with dementia and cognitive impairment because of adverse CNS effects.
Particular caution should be used in patients with dementia. According to a Cochrane systematic review, there is a lack of randomized controlled trials of benzodiazepine or nonbenzodiazepine hypnotics in patient with Alzheimer's dementia (AD). Studies of melatonin, either immediate- or slow-release, did not show an improvement of sleep parameters in patients with AD while a small randomized trial of trazodone 50 mg qHS for two weeks improved nocturnal total sleep time and sleep efficiency without serious side effects.[75]
There are several medications used in the treatment of sundowning including melatonin, antipsychotics, antidepressants, benzodiazepines, and cannabinoids. While commonly used, there is little evidence to suggest benefits associated with the use of benzodiazepines and cannabinoids, and due to the significant negative side effects associated, the use of these agents should be avoided.[76, 77, 78] Antipsychotics are commonly used and are recommended as possible treatments in national guidelines, yet there are only limited data that show minimal benefits for these patients.[79, 80] There have been few double-blind, randomized controlled trials evaluating the use of exogenous melatonin.[81] Overall, these studies show some behavioral improvement with extended use.[82] Melatonin dosage widely varied in these studies between 1.5 mg and 10 mg. Several non-pharmacological strategies have been used and have shown to have some beneficial impact on circadian rhythm and possibly nighttime behavioral disturbances in patients with dementia including cognitive training,[83] physical exercise,[84, 85] aromatherapy[86, 78] music therapy,[87, 78] and bright light therapy.[88, 78] Three treatment principles are suggested when considering treatments for sundown syndrome: (1) the treatment process is a trial-and-error approach, (2) start with lower dosages and slowly titrate upwards, and (3) multi-component therapy (non-pharmacological and pharmacological) may be indicated.[89] Further investigation of non-pharmacological and pharmacological-targeted strategies would be of benefit.[90]
In a 2017 phase III randomized double-blind placebo-controlled parallel-group trial, the orexin receptor antagonist suvorexant was found to be effective in regard to improving sleep onset and maintenance over 3 months of nightly treatment in older adult patients with insomnia.[91] Moreover, a 2019 case-series study found suvorexant to effectively manage nocturnal delirium / Sundown syndrome in 4 patients with moderate to severe Alzheimer’s disease.[92] Additional follow-up studies are needed to better understand suvorexant’s clinical efficacy in sundowning.
Clinical Context: Zolpidem is structurally dissimilar to benzodiazepines but similar in activity, with the exception of having reduced effects on skeletal muscle and seizure threshold. At recommended doses, it is as effective as triazolam. Adverse CNS effects (eg, nightmares, agitation, drowsiness) have been noted in 10% of patients. In May 2013 the FDA warned that patients taking zolpidem extended release (6.25 mg or 12.5 mg) should not drive or engage in other activities that require full alertness the day after taking the drug. As with benzodiazepine hypnotics, zolpidem is approved only for short-term use (maximum, 3-4 weeks); if used longer, they should be used for only 2-3 nights per week and for no more than 3 months.
Clinical Context: Zaleplon is a short-acting pyrazolopyrimidine hypnotic with full agonistic activity on central benzodiazepine receptors (B21 type). It has a short half life (1 hour) and at small doses, it is an effective sleep inducer. It is approved only for short-term use (maximum, 3-4 weeks); if used longer, it should be limited to only 2-3 nights per week and for no more than 3 months.
Clinical Context: Eszopiclone is a nonbenzodiazepine hypnotic pyrrolopyrazine derivative of the cyclopyrrolone class. The precise mechanism of action is unknown but is believed to be an interaction with the GABA-receptor at binding domains close to or allosterically coupled to benzodiazepine receptors. It is indicated for insomnia to decrease sleep latency and improve sleep maintenance. Eszopiclone has a short half-life, of 6 hours. Higher doses (ie, 2 mg for elderly adults and up to 3 mg for nonelderly adults) are more effective for sleep maintenance, whereas lower doses (ie, 1 mg) are more suitable for difficulty in falling asleep.
Barbiturates are not indicated for insomnia, and psychiatric consultation may become necessary for patients receiving barbiturates for many years. Barbiturates are effective only for short-term use, losing much of their effectiveness after 2 weeks of administration.
Clinical Context: Doxepin at low doses (1, 3, and 6 mg) is a selective histamine antagonist (primarily H1 receptor) and is FDA approved for insomnia. Recent studies have shown that low-dose doxepin improves sleep parameters in older adults with a safety profile comparable to placebo. Higher doses of doxepin should be avoided in older adults because of high anticholinergic side effects. Avoid in patients with glaucoma or urinary retention.
Clinical Context: Mirtazapine exhibits both noradrenergic and serotonergic activity. In cases of depression associated with severe insomnia and anxiety, mirtazapine has been shown to be superior to other SSRIs.
Clinical Context: Trazodone is an antagonist at the 5-HT2 receptor and minimally inhibits the reuptake of 5-HT. It has negligible affinity for cholinergic and histaminergic receptors. Trazodone is not associated with tolerance or withdrawal effects but it may prolong the QTc interval. Associated orthostatic hypotension can be minimized by administration with food. Limited data exist regarding efficacy in patients without depression, and the FDA has not approved trazodone as a hypnotic.
Sedating antidepressants like trazodone and mirtazapine in low doses are often prescribed at bedtime for insomnia. Little scientific evidence supports efficacy in the treatment of insomnia without associated depression; their use in patients with insomnia without depression is not FDA approved and should be considered off-label use. Doxepin is the only antidepressant, which, at a very low dose, is FDA approved for insomnia.
Clinical Context: Ramelteon is a melatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep and be involved in maintaining circadian rhythm and a normal sleep-wake cycle. Ramelteon does not cause rebound insomnia or withdrawal symptoms at discontinuation. It is approved for prolonged use. It is indicated for insomnia characterized by difficulty with sleep onset.
Clinical Context: Suvorexant is an orexin receptor antagonist. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R by suvorexant is thought to suppress wake drive. It is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance. Adverse effects include residual daytime sedation.
Orexin promotes wakefulness. Antagonism of the orexin receptor suppresses this action by orexin.